Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-08-27 to 2003-09-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study performed according to OECD guideline 402 and EU directive B.3. No deviations were recorded.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): T002251
- Substance type: Brown powder
- Physical state: solid
- Analytical purity: 96%
- Purity test date: no data
- Lot/batch No.: 00410155
- Expiration date of the lot/batch: 2004-05-05
- Stability under test conditions: Unknown in PEG 300.
- Storage condition of test material: In the original container, at room temperature (range of 20 +/- 3 °C), away from direct sunlight.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HanBrl:Wist (SPF) from RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf, Switzerland.
- Age when treated: Males 8 weeks; Females 12 weeks.
- Weight at 1st day of treatment: Males: 235.6 - 254.1g; Females: 182.4 - 199.2g
- Fasting period before study:no data
- Housing: Standard Laboratory conditions; during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation
- Diet: ad libitum, pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet
- Water: ad libitum, community tap water from Füllinsdorf
- Acclimation period: at least 7 days, under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30- 70 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12
- Other: Music during light period

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on dermal exposure:
TEST SITE
- Area of exposure: back of the animal
- % coverage: 10% of total body surface
- Type of wrap if used: semi-occlusive dressing which was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm tap water and dried with disposable paper towels
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4ml/kg body weight
- Concentration (if solution): 0.5 g/ml
- Constant volume or concentration used: yes


VEHICLE (PEG300)
- Amount(s) applied (volume or weight with unit): 4ml/kg
- Concentration (if solution): 0.5 g/ml
- Lot/batch no. (if required): 448174/1 21203148
- Purity: no data
- justification of selection: the vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females (total 10 animals)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality / Viability: Dailing during acclmatization and twice during days 1-15.
- Necropsy of survivors performed: yes, all animals were killed at the end of the observation period by an intraperitoneal injection of Vetanarcol at a dose of at least 2.0 mL/kg bodyweight (equivalent to at least 324 mg sodium pentobarbitone/kg body weight) and discarded after macroscopic examinations were performed. No organs or tissues were retained.
- Other examinations performed: clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15; Body weights: on test days 1 (prior to administration), 8 and 15; organ weights, histopathology, other:
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured during the study.
Clinical signs:
No clinical signs were observed during the course of the study. Slight brown discoloration produced by the test item was observed in all male and female animals on test days 2 and 3.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of T002251 after single dermal administration to rats of both sexes, obeserved over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight. Therefore T002251 does not need to be classified, based on CLP regulation.